This invention relates to an artificial blood vessel comprising a vessel wall that is porous as a whole, having an innermost layer capable of maintaining a long-term patency, having a property of being readily pierced with a suturing needle, and having durability to repeated needling, being free of permeation of blood from the vessel wall; and a process for preparing the same.
Transplantation of an artificial blood vessel to a living body causes initial thrombi on the inner surface that comes in contact with blood, and cells propagate themselves thereon to form a neointima, which becomes an antithrombotic intimal tissue. Thus, the artificial blood vessel can not play a role as a living body substitute before the inner wall of the blood vessel turns to part of the living body.
For this purpose, there is an artificial blood vessel in which an innermost layer of the inner surface side has been made porous so that such an intima can be effectively formed (Japanese Unexamined Patent Publication No. 22571/985).
However, even though the innermost layer is made porous, formed on the inner surface are nothing more than mere concaves if its pores are of mutually closed structure. This may result in a lowering of the tissue coaptation between the inner surface and intimal tissues or granulation tissues. In particular, the peeling-off of granulation tissues at an anastomosed portion may result in further growth of the granulation tissues to bring about excessive formation thereof (i.e. panni), thus causing obturation of a blood vessel at that part.
As stated above, the artificial blood vessel in which the innermost layer of the inner surface side has been merely made porous can not maintain a long-term patency because of weakness in the tissue coaptation, and any blood vessels having an inner diameter of 6 mm or less, particularly 4 mm or less, have been unable to be put into practical use.
The artificial blood vessel is also required, in view of readiness in operations, to have a property of being readily pierced with a suturing needle when anastomosed to a living body blood vessel. On the other hand, needling is so frequently repeated in blood access for use in blood dialysis, which is used in connecting arteries and veins, that the vessel wall is required to be durable to repeated needling, and also impermeable to blood so that there may be produced no hematoma or seroma (serum tumor) accompanying bleeding after needling.
Here, what is meant by "impermeable to blood" is that application of inner pressure of 450 mmHg to an artificial blood vessel may not result in permeation of plasma.
Available as an artificial blood vessel that may satisfy such a requirement is the one disclosed in Japanese Unexamined Patent Publication No. 150954/1982. This artificial blood vessel, however, has a dense layer, homogeneous and containing no vacuoles of at least 0.1 .mu.m or more in diameter, obtained by coating a solution of a polymeric compound on a rod-like mold followed by drying and then desolvation.
For this reason, its vessel wall becomes rigid, and, even when its layer has a thickness, for example, of about 5 .mu.m, extremely impedes the passing-through of a suturing needle to make it difficult to carry out an operation. As a result, the bleeding tends to stop with difficulty owing to repeated needling, causing generation of seromas, or resulting in protrusion of a cut-end surface of a living body blood vessel to the lumen side of the part anastomosed to a living body blood vessel to cause growth of panni. Disturbance at the inside may also cause a turbulent flow and partial stagnation of blood, causing the formation of thrombi.
Accordingly, in order to suppress the obturation due to the initial thrombi formed on the inside after transplantation, it is important for the vessel wall not only to be made of a antithrombotic material but also not to have such a dense layer.
Moreover, such a dense layer should preferably not exist also in order to suppress the obturation of a lumen caused when the artificial blood vessel is folded, i.e., the kinking.
As mentioned above, in the conventional artificial blood vessels, nothing has been available that has a property of being readily pierced with a suturing needle, has durability to repeated needling, and yet has a superior non-permeability to blood.
As a method of preparing an artificial blood vessel comprising a porous vessel wall, disclosed, for example, in Japanese Unexamined Patent Publications No. 81349/1982 and No. 1,881,651,985 is a method in which a material solution obtained by previously mixing and dispersing a pore-forming agent in a polymeric compound is formed and thereafter said pore-forming agent is removed. However, this conventional method, in which the pore-forming agent is used, has the following problems.
First, when the pore-forming agent is added in an excessively small amount, the vessel wall can not be made porous and only formed with unevenness on the surface because of the pore-forming agent remaining unremoved even by removing operation. On the other hand, when the pore-forming agent is add in an excessively large amount (e.g. an amount of more than 30 to 40% based on the weight of the polymeric compound), the mixed solution loses its fluidity, thus not only making it difficult to carry out forming treatment or surface treatment, but also resulting in cracks formed on the surface of the resulting artificial blood vessel or unevenness in thickness. In such an occasion, even if it is attempted to forcibly add 50% by weight of the pore-forming agent, there can be achieved a porosity of usually from 0.5 to 0.7 in approximation at best, which porosity is determined by the formula: apparent density/density of raw material (hereinafter the porosity is calculated in the same manner).
If it is attempted to solve the above problem by mixing the pore-forming agent in an amount of about 20% by weight, the pore-forming agent and the polymeric compound can not be uniformly dispersed, so that there can be formed only a product having a non-uniform pore distribution in the resulting vessel wall.
As discussed above, the conventional methods employing the pore-forming agent can not obtain artificial blood vessels having uniform porous structure, particularly artificial blood vessels of open-cell structure.